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Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis.

ABSTRACT: Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression toward metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGF? and direct platelet-tumor cell contacts synergistically activate the TGF?/Smad and NF-?B pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-?B signaling in cancer cells or ablation of TGF?1 expression solely in platelets protects against lung metastasis in vivo. Thus, cancer cells rely on platelet-derived signals outside of the primary tumor for efficient metastasis.

SUBMITTER: Labelle M

PROVIDER: S-EPMC3487108 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis.

Labelle Myriam M Begum Shahinoor S Hynes Richard O RO

Cancer cell 20111101 5

Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression toward metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGFβ and direct platelet-tumor cell contacts synergistically activate the TGFβ/Smad and NF-κB pathwa ...[more]

PMID: 22094253

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Direct Signaling Between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis

Project description:Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression towards metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we show that transient platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGF-beta and direct platelet-tumor cell contacts synergistically activate the TGF-beta/Smad and NF-kappaB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-kappaB signaling in cancer cells or ablation of TGF-beta1 expression solely in platelets protects against lung metastasis in vivo. Thus, cancer cells rely on platelet-derived signals outside of the primary tumor for efficient metastasis. MoEx-1_0-st: Five replicates of Ep5 tumor cells cultured alone, five replicates of tumor cells cultured in combination with platelets, and three replicates of tumor cells combined with platelets just prior to RNA isolation to control for the presence of platelet RNAs. MoGene-1_0-st: Three replicates of tumor cells cultured alone, three replicates of tumor cells cultured in combination with platelets, three replicates of tumor cells cultured with centrifuged platelets and three replicates of tumor cells cultured with supernate (releasate) from centrifuged platelets.

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Direct Signaling Between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis

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